EX-10 2 ex10-1.txt RESEARCH AGREEMENT EXHIBIT 10.1 RESEARCH AGREEMENT EXHIBIT 10.1 RESEARCH AGREEMENT WHEREAS: This contract is entered into between Xpention Genetics, Inc., a company organized under the laws of Nevada, having its business office at 10965 Elizabeth Drive, Conifer, CO. 80433 ("XPENTION") and The University of Texas Health Science Center at San Antonio ("UTHSCSA"), 7703 Floyd Curl Drive, San Antonio TX 78229-3900, a component of The University of Texas System ("System"). THEREFORE: In consideration of the foregoing and the mutual promises, covenants and agreements herein set forth, XPENTION and UTHSCSA agree as follows: 1. Scope of Work UTHSCSA agrees to perform for XPENTION the research activities for the project entitled "Development of the p65 Immunological Test" described in Attachment A hereto. 2. Contract Period This contract shall become effective on December 1, 2005, and shall be completed on June 30, 2006 unless subsequent time extension, supplement, addition, continuation or renewal is mutually agreed upon in writing between the parties. 3. Standard of Performance UTHSCSA shall perform the Work in a manner consistent with the highest standards of scientific and professional skill and in accordance with the terms and conditions of this Agreement. Margaret Hanausek, Ph.D. , UTHSCSA's designated Principal Investigator for the project (the "PI"), shall monitor UTHSCSA's performance hereunder and shall notify XPENTION of UTHSCSA's failure to comply with the terms of this Agreement within a reasonable time after UTHSCSA learns of such failure. 4. Assignment Neither party shall assign or transfer any interest in this agreement, nor assign any claims for money due or to become due under this agreement without the prior written approval of the other party. 1 5. Payments to Subcontractor The cost for UTHSCSA's completion of the Work, including indirect charges, is $64,306. Payments by XPENTION to UTHSCSA shall be made in accordance with the following schedule: a. Signature: $34,306 b. 4 month mark: $20,000 c. Final report submission: $10,000 Payments will be effected within 45 days of receipt of invoice. 6. Indemnification XPENTION agrees to indemnify and hold The University of Texas System ("System"), UTHSCSA, their Regents, officers, agents and employees harmless from any liability, loss or damage they may suffer as a result of claims, demands, costs or judgments against them arising out of the activities to be carried out pursuant to the obligations of this Agreement, including, but not limited to, the use by XPENTION of the results obtained from the activities performed by UTHSCSA under this Agreement; provided, however, that any such liability, loss or damage resulting from the following subsections is excluded from this Agreement to indemnify and hold harmless: a. the negligent failure of UTHSCSA to substantially comply with any applicable FDA or other governmental requirements; or b. the negligence or willful malfeasance of any Regent, officer, agent or employee of UTHSCSA or System. 7. Publications UTHSCSA shall be sited in all research reports and other publications relating to the work under this Agreement. 9. Law This Agreement is entered into pursuant to and under the authority granted by the laws of the state of Texas and any applicable federal laws. The provisions of this Agreement shall be construed to conform to those laws. 2 10. Termination This Agreement may be terminated by either of the parties hereto upon written notice delivered to the other party at least thirty (30) days prior to intended date of termination. By such termination, neither party may nullify obligations already incurred for performance or failure to perform prior to the date of termination. 11. Changes and Amendments This contract constitutes the entire agreement between the parties. All amendments and /or changes shall be by written instrument executed by the parties hereto. 12. Intellectual Property The parties acknowledge that portions of this research may utilize intellectual property addressed by the following US patents which are licensed to XPENTION by the Board of Regents of The University of Texas System: o US Patent # 5,310,653 (May, 1994) o US Patent # 5,411,868 (May, 1995) o US Patent # 5,773,215 (June, 1998) All additional intellectual property, if any, which is developed through this research, shall be governed by The Rules and Regulations of the Board of Regents of The University of Texas System for the Government of The University of Texas System, and according to US patent law. IN WITNESS WHEREOF, the parties hereto have caused this contract to be executed as of the date set forth herein by their duly authorized representatives.
THE UNIVERSITY OF TEXAS HEALTH XPENTION GENETICS, INC. SCIENCE CENTER AT SAN ANTONIO /s/ Jane A. Youngers 12/12/05 /s/ David Kittrell 12/20/05 ------------------------------------------ ---------------------------------------- Jane A. Youngers Date David Kittrell Date Assistant Vice President for Research President and CEO I have read this agreement and understand my obligations hereunder. /s/ Margaret Hanausek 12/12/05 ------------------------------------------ Margaret Hanausek, Ph.D. Date Principal Investigator
3 ATTACHMENT A SCOPE OF WORK THE P65 ONCOFETAL PROTEIN AS A NOVEL TUMOR MARKER IN DETECTION OF BREAST, PROSTATE AND OTHER CANCERS Margaret Hanausek, Ph.D., Principal Investigator The University of Texas Health Science Center at San Antonio David Kittrell, CEO Xpention Genetics Inc Conifer, CO 80433 The proposed research will focus on a novel oncofetal protein with a molecular weight of 65 kDa (p65). The development of intermediate biomarkers of cancer risk and or cancer presence and the evaluation of efficacy of individual biological or molecular markers is an important avenue in cancer research. The protein we are studying (p65) appears to have all the characteristics of such a marker. Our ultimate goal is to prove usefulness of p65 in early detection and management of different human cancers, including breast and prostate cancer. The p65 gene is a novel member of the steroid receptor super-family of genes. The overall objective is to identify the cellular origin of p65 and elucidate the mechanisms of its expression in rodent and or mammalian (i.e. canine) liver, skin, colon, prostate, and mammary gland carcinogenesis as well as in the development of lymphomas and leukemias, and combine these basic studies with the translational research to provide better understanding of the role of this novel tumor marker in cancer development. Malignant tumors appear to universally produce the oncofetal protein, p65. In addition, p65 is expressed very early during the carcinogenesis process. It is a shedding antigen and can be found in the blood (plasma/serum) of tumor-bearing animals, as well as in the plasma/serum of cancer patients. This fact suggests that p65 antibodies may be useful in human cancer screening, carcinogenesis studies and studies on cancer risk assessment. The most striking observation made during development of monoclonal antibodies and establishing ELISA for p65, was that the monoclonal antibodies directed against p65, detect with a great accuracy human cancers such as breast, prostate and colon cancer. We have now identified the p65 gene as a novel member of the super-family of genes that encode nuclear receptors for various hydrophobic ligands such as steroids, vitamin D, retinoic acid, and thyroid hormones. These receptors are composed of 1 several domains important in hormone binding, DNA binding, dimerization, and transcription activation. The human p65 cDNA was recently cloned, revealing at its C-terminal end regulatory elements typical of this super-family of genes. Using ELISA, p65 was shown to be a promising marker for diagnosis and prognosis of breast cancer. Cancer is commonly encountered in pet animal practices and is one of the leading causes of pet death. While the pet's prognosis is dependent upon various factors including tumor type and stage at diagnosis, for the vast majority of cancers, early detection and treatment are extremely important in successful cancer therapy. Although various tumor markers have been shown to be useful diagnostic and prognostic indicators in human oncology, their application to companion animal medicine has barely been explored. The ideal tumor marker would be produced only by malignant cells, be detectable early after the onset of tumor formation, and have levels that directly correlate with tumor burden. Our preliminary studies with a 65-kD tumor-associated protein (p65), in spontaneous canine lymphosarcoma cases and experimentally induced malignancies in rodent models indicate that this tumor marker possesses these ideal characteristics and has great potential utility in companion animal cancer medicine. We have developed a test for veterinary application in the differential diagnosis of malignancy, in assessing patient response to cancer therapy, and in monitoring clinical remission to enable the prompt detection of cancer recurrence using double sandwich ELISA with monoclonal and polyclonal antibodies to p65. This study will focus on the characterization, detection method development, and clinical analysis of a unique 65-kD tumor-associated tumor marker in canine cell line products and in stored plasma collected from different canine cancer cases. The project's overall objective will be the development of a quantitative assay for the p65 tumor marker in the dog. In order to attain our overall objective we will first obtain p65-specific peptides. Purified p65 peptides will then be used as source material to obtain monoclonal antibodies and or monospecific antibodies to detect cancer in dogs. Carefully designed molecular biology and human studies will then follow. The following milestones are planned: 2 1. We will design synthesis of 15-18 amino acids (2 sets one from NH2 end and one from C-terminus end) that will serve as primers for monoclonal and monospecific antibodies. Since the primers are relatively short, it will be necessary to conjugate them with KLH (keyhole limpet hemocyanin [KLH] protein) to increase the size of the antigen and its immunogenicity before injecting mice. 2. We have selected New England Peptide Co. to make both sets of anti- bodies. The time frame for this work is 3-6 months. The company will synthesize peptides, conjugate them with KLH, inject mice, as routinely is done for such projects, and provide us with sera contain -ing anti-p65 antibodies. 3. When we receive sera plus peptides as standards, we will start work on the characterization of the antibodies and designing ELISA work. This step will require 2-3 months. 4. We will receive blood specimens from different canine cancer subjects from Dr Susan Lana, Colorado State University at Fort Collins, Animal Cancer Center. These samples will be taken prior to any cancer treatment and will include a variety of cancer types and a small number of normal dogs. Once the antibodies are available the blood samples will be tested. This will constitute the first phase of this project. Future work may entail collection of more specific samples such as post treatment or at the time of disease progression. 3